NSTEMI algorithm, metabolic acidemia, and more

Summaries from ACP Hospitalist Weekly.

Rapid rule-out algorithm for NSTEMI deemed safe, effective

The European Society of Cardiology (ESC)'s algorithm for rapid rule-out and rule-in
of non-ST-segment elevation myocardial infarction (NSTEMI) using high-sensitivity
cardiac troponin appears safe and effective in triaging patients, a large multicenter
study found.

Researchers prospectively enrolled patients in six countries who presented to the
ED with symptoms of NSTEMI from May 2006 to April 2016. High-sensitivity cardiac troponin
T (hs-cTnT) and high-sensitivity cardiac troponin I (hs-cTnI) were measured at presentation
and after one hour. The ESC hs-cTn 0/1-h algorithm uses assay-specific cutoff levels for hs-cTnT and hs-cTnI, in conjunction with other clinical information such as clinical assessment and electrocardiography,
to triage patients very early to rule out or rule in myocardial infarction. In the
current study, negative predictive value (NPV) for NSTEMI was used to quantify rule-out
safety, positive predictive value (PPV) was used to quantify rule-in accuracy, and
the proportion of patients triaged within one hour was used to quantify overall efficacy.
Results were published Aug. 7, 2018, issue of the Journal of the American College of Cardiology.

Image by Getty Images

NSTEMI prevalence was 17%. Among 4,368 patients for whom hs-cTnT measurements were
available, safety of rule-out (NPV, 99.8%; 2,488 of 2,493 patients), accuracy of rule-in
(PPV, 74.5%; 572 of 768 patients), and overall efficacy were high, with three-fourths
of patients assigned either to rule-out (57%; 2,493 of 4,368 patients) or rule-in
(18%; 768 of 4,368 patients). Among 3,500 patients for whom hs-cTnI measurements were
available, safety of rule-out (NPV, 99.7%; 1,528 of 1,533 patients), accuracy of rule-in
(PPV, 62.3%; 498 of 800 patients), and overall efficacy were high, with more than
two-thirds of patients assigned either to rule-out (44%; 1,533 of 3,500 patients)
or rule-in (23%; 800 of 3,500 patients). The researchers noted that excellent safety
was confirmed in multiple subgroup analyses including patients who presented three
hours or less after chest pain onset.

All diagnostic algorithms based on high-sensitivity cardiac troponin should always
be used in conjunction with all other information available to the clinicians, including
vital signs, 12-lead electrocardiogram, and chest pain characteristics, the authors
wrote.

“The combination of the ESC 0/1-h algorithm with quantified clinical judgment
seems particular[ly] valuable, as it has been shown to help identify patients with
UA [unstable angina], the more benign acute coronary syndrome phenotype. Moreover,
it is important to mention that beyond the ESC 0/1-h algorithm, other early biomarker-based
strategies also have been developed and seem to justify clinical use,” the
authors wrote.

“Even then, however, caution is advised when dealing with patient subsets such
as the elderly, the critically ill, individuals with end-stage renal disease, those
who present with atypical symptoms, and perhaps also those who present very early
after the onset of symptoms,” the editorial cautioned. “It is likely
for these reasons and others that an independent evaluation employing this approach
in an emergency medicine setting performed far less well than in the present study.”

Sodium bicarbonate did not improve survival in ICU patients with metabolic acidemia

Receiving sodium bicarbonate did not affect overall survival in ICU patients with
severe metabolic acidemia, but it did appear to improve outcomes in the subgroup of
patients with acute kidney injury, a recent study found.

The study's primary outcome was a composite of death from any cause by day 28 and
the presence of at least one organ failure at day 7. It occurred in 71% of the control
group compared to 66% of the bicarbonate group (absolute difference estimate, −5.5%;
95% CI, −15.2 to 4.2; P=0.24). Using the Kaplan-Meier method to estimate probability of survival, the researchers
found no significant difference overall (46% in controls vs. 55% in bicarbonate patients; P=0.09), but sodium bicarbonate was associated with significantly better survival in
a prespecified subgroup of patients with Acute Kidney Injury Network (AKIN) scores
of 2 or 3 (63% vs. 46%; P=0.0283). Metabolic alkalosis, hypernatremia, and hypocalcemia were more common in
the bicarbonate group, but no life-threatening complications were reported.

The study authors noted that sodium bicarbonate was also associated with less renal
replacement therapy, and they speculated that the reduced mortality among patients
with acute kidney injury might have resulted from having more days free of vasopressor
and renal replacement therapy than controls. This and other studies support the importance
of sodium bicarbonate timing, the authors said, noting that almost none of the patients
were given sodium bicarbonate after the first 24 hours and that “sodium bicarbonate
infusion might have bought time” to avoid or delay renal replacement therapy.
Limitations included that no specific control solution was recommended, and future
research should look at whether different formulas for sodium bicarbonate infusion
affect outcomes.

Infective endocarditis risk increased after many types of medical procedures

A recent study found evidence of an association between several medical procedures
and the development of infective endocarditis.

The study included all adult patients treated for endocarditis at hospitals in Sweden
between Jan. 1, 1998, and Dec. 31, 2011, for a total of 7,013 cases of infective endocarditis.
Using a case-crossover design, the authors compared invasive medical procedures in the 12 weeks before patients developed endocarditis with a corresponding 12-week period in the same patients exactly one year earlier.
Results were published by the Journal of the American College of Cardiology on June 11, 2018.

A significantly increased risk for infective endocarditis was found after certain
cardiovascular procedures (particularly coronary artery bypass grafting), procedures
involving the skin and management of wounds, transfusion, dialysis, bone marrow puncture,
and some endoscopies (particularly bronchoscopy). This large study “suggests
that several invasive nondental medical procedures are associated with a markedly
increased risk for infective endocarditis,” the authors concluded.

The authors noted that the use of prophylactic antibiotics before procedures has been
discouraged in recent years. They calculated that, based on the study, 476 patients
undergoing high-risk medical procedures would need to receive antibiotics to prevent
one case of infective endocarditis. If prophylactic antibiotics were more narrowly
targeted at particularly high-risk procedures, the number needed to treat could be
lower (83 for bronchoscopy, for example). These calculations are based on antibiotics
providing perfect protection against infective endocarditis and so would not be entirely
accurate in real-world practice, the authors cautioned.

The study results could also encourage improvement of aseptic measures before and
during procedures, consideration of the costs and benefits of elective procedures
for patients at high risk, and earlier identification of infective endocarditis after
procedures, the study authors said.

An accompanying editorial comment cautioned that observational data do not prove causality but agreed that the study “reopens the debate on the role of invasive medical
procedures as a trigger for infective endocarditis.” The editorialists recommended
a response focused on infection avoidance. “At least for those procedures where
sterility should be easy to achieve and maintain, the solution is more likely to lay
with improved sterile technique, infection control procedures and identifying systematic
approaches for reducing health care-associated bacteremia rather than necessarily
advocating antibiotic prophylaxis,” they wrote.

Patients who experience an acute exacerbation of chronic obstructive pulmonary disease
(COPD) may be at increased risk for a subsequent cardiovascular event, according to
a recent study.

Researchers performed a case-series analysis of data from patients in three U.S. states
from 2005 through 2011 who were at least 40 years of age and had an acute COPD exacerbation.
The goal of the study was to determine whether an acute exacerbation was associated with acute cardiovascular event incidence at 30 days and one year. The primary outcome measure was a composite of an ED visit
or nonelective hospitalization for an acute cardiovascular event (acute myocardial
infarction, heart failure, atrial fibrillation, pulmonary embolism, and stroke). Incidence
rate ratios (IRRs) were estimated for acute cardiovascular event incidence in the
30-day period before the index exacerbation and the 30 days afterward, as well as
for the one-year period after the index exacerbation versus the one-year period before
it. Study results were published online June 8, 2018, by the Journal of General Internal Medicine and appeared in the September 2018 issue.

The study included 362,867 patients who had an ED visit or hospitalization for an
acute COPD exacerbation. Median age was 70 years, 57% of patients were women, and
71% were of non-Hispanic white ethnicity. The incidence of acute cardiovascular events
was significantly higher in the 30 days postexacerbation versus the 30-day reference
period (IRR, 1.34; P<0.001) and in the year postexacerbation versus the one-year reference period
(IRR, 1.20; P<0.001). This association between an acute COPD exacerbation and an acute cardiovascular
event persisted for each cardiovascular condition separately (P<0.05 for all).

The researchers noted that administrative data could have misclassified some hospitalizations
and that the databases used did not include information on clinical variables such
as chronic COPD severity, among other limitations. However, they concluded that an
association exists between acute COPD exacerbation and increased incidence of a subsequent
acute cardiovascular event at 30 days and one year.

“Our findings should encourage researchers to elucidate the mechanisms linking
[acute exacerbation of COPD] to the development of cardiovascular events,”
the authors wrote. “For clinicians, our data support an importance of [acute
exacerbation of COPD] as an opportunity to implement cardiovascular prevention measures
in this high-risk population.”

Patients with elevated D-dimer levels at admission for acute heart failure had increased short-term risk of
ischemic stroke, according to a recent study.

The retrospective registry study included 721 consecutive patients hospitalized for acute heart failure between January 2013 and May 2016 at
a single center in Japan. All had their plasma D-dimer levels measured on admission. The patients' mean age was 76 years, 60% were
men, and 54% had atrial fibrillation. The mean left ventricular ejection fraction
was 38%, and the median length of hospitalization was 21 days. Compared to a normal D-dimer level of less than 1.0 µg/mL, the patients' median level on admission
was 2.1 µg/mL (interquartile range, 1.1 to 4.2 µg/mL). Results were
published by Stroke on June 7, 2018, and appeared in the July 2018 issue.

An ischemic stroke occurred during hospitalization in 18 patients (2.5%), and 16 patients
(2.2%) had an ischemic stroke within 30 days. The study found the optimal D-dimer cutoff value for the risk of stroke in the hospital or within 30 days was 3.5
µg/mL. No patients with a D-dimer level less than the reference limit of normal (1.0 µg/mL) had a stroke.
A higher D-dimer level on admission was an independent determinant of risk of in-hospital ischemic
stroke even after adjustment for CHA2DS2-VASc score (odds ratio [OR], 2.29; 95% CI, 1.46 to 3.60; P<0.001) and major confounders, including age, atrial fibrillation, and antithrombotic
therapy (OR, 2.31; 95% CI, 1.43 to 3.74; P<0.001). The results were similar in the subgroups of patients without atrial
fibrillation (OR, 2.46; 95% CI, 1.39 to 4.54; P=0.002) and those not on antithrombotic therapy (OR, 2.79; 95% CI, 1.53 to 5.57; P<0.001) and when 30-day risk of stroke was the outcome.

The results suggest that a high D-dimer level at admission may be useful to identify patients with acute heart failure
who have high thromboembolic risk, and conversely, that a normal level may exclude
short-term risk of stroke, the study authors said. They noted that the study found
high risk of thromboembolism in the immediate period after an acute heart failure
event and thus, “risk stratification for short-term ischemic stroke events
is strongly warranted for the management of hospitalized patients with [acute heart
failure].”

Current guidelines do not recommend routine antithrombotic therapy for patients with
heart failure without atrial fibrillation, said the authors, who suggested that biomarkers
like D-dimer could potentially be used to identify patients who would benefit. Limitations
of the study include that it was conducted at a single center with a relatively small
sample size and that it was retrospective, with the use of antithrombotic therapy
decided by the treating physicians.

Patients reported sleeping 83 minutes less in the hospital than at home (95% CI, 75
to 92 minutes; P<0.001). Their mean number of nocturnal awakenings was 2.0 (95% CI, 1.9 to 2.1)
at home versus 3.3 (95% CI, 3.2 to 3.5) in the hospital (P<0.001). The patients woke up 44 minutes earlier than they habitually did at home.
More than two-thirds (70.4%) reported having been awakened by external causes, a third
(35.8%) of which involved hospital staff. The most reported sleep-disturbing factors
were noise of other patients, medical devices, pain, and toilet visits.

“Most of the sleep-disturbing factors found in our study seem easy to address
by incorporating simple changes in nightly hospital routines,” the study authors
said. Interventions such as dimmed hallway lights, silent footwear, remote alarms,
earplugs, and eye masks can minimize noise and light disturbances, the authors noted.
In addition, changing the timing of nursing activities, avoiding unnecessary procedures
overnight, and minimizing continuous overnight IV drips and afternoon diuretics could
potentially help and should be tested in prospective studies, the authors said.

They did note limitations to the study, including that almost one-third of surveyed
patients had to be excluded due to missing data, including 41 patients who reported
not to have slept at all. In addition, some patients weren't surveyed because they
had delirium or cognitive problems or were asleep when the questionnaires were distributed.

The study found that intraoperative hypotension was significantly less frequent in
the omission group than the continuation group (55% vs. 69%; relative risk [RR], 0.81;
95% CI, 0.67 to 0.97; P=0.03; number needed to harm, 7.5). Postoperative hypotension, defined as an SBP under
90 mm Hg, was also less frequent in the omission group (RR, 0.49; 95% CI, 0.28 to
0.86; P=0.02), although the authors noted that the study was not powered to measure postoperative
outcomes. Postoperative hypertension, defined as an SBP above 180 mm Hg, was more
frequent in the omission group than in the continuation group (RR, 1.95; 95% CI, 1.14
to 3.34, P=0.01).

Finding less intraoperative hypotension with omission of an ACE inhibitor before surgery
is in accordance with previous randomized trials, the study authors said. “These
findings, while at odds with current [American College of Cardiology/American Heart
Association] guidelines, align with the findings of a meta-analysis on this subject
and with recent literature,” they wrote.

The study had a number of limitations, including variation in which ACE inhibitor
was given and the timing of the last dose before surgery, the authors said. The postoperative
findings also conflict with some previous research and they were not associated with
any change in adverse events, the authors noted. They called for future research in
this area to include clinically important endpoints.

Reducing intraoperative hypotension will not necessarily reduce adverse events, an accompanying editorial
said. The editorialist noted controversy and variation in guidelines and policies on perioperative
management of renin-angiotensin inhibitors. “Overall, perioperative physicians
should now adopt the standard approach of temporarily withdrawing renin-angiotensin
inhibitor therapy 24 hours before major inpatient noncardiac surgery. Nonetheless,
they should do so cautiously, recognizing that the data underpinning this strategy
remain weak,” the editorial said.

These summaries come from ACP Hospitalist Weekly, an e-newsletter provided every Wednesday by ACP Hospitalist. To receive it, call Customer Service at 800-543-1546, ext. 2600, or direct at 215-351-2600
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Guideline corner: Antithrombotic therapy for afib

The guidelines are based on systematic reviews and meta-analyses of the literature
published since development of the previous guidelines, which were published in 2012.
Overall quality of the evidence was assessed by using the GRADE (Grading of Recommendations,
Assessment, Development, and Evaluation) approach, and recommendations were finalized
based on the consensus of the expert panel. The guidelines were published Aug. 22,
2018, by CHEST and appeared in the November 2018 issue.

The guidelines include 60 recommendation statements for patients at varying levels
of stroke risk and for several clinical scenarios in the areas of stroke risk, bleeding
risk, antithrombotic therapy and other methods of stroke prevention, adjusted-dose
oral vitamin K antagonist (VKA) therapy, and management of bleeding on oral anticoagulation,
among other topics. In a press release, the American College of Chest Physicians identified
the following as key recommendations that differed from previous guidelines:

No antithrombotic therapy is suggested in patients with atrial fibrillation without
valvular heart disease, including those with paroxysmal atrial fibrillation who are
at low stroke risk.

For patients who have one non-sex CHA2DS2-VASc stroke risk factor and for patients who are at high risk for stroke, oral anticoagulation
is suggested rather than no therapy, aspirin, or combination therapy with aspirin
and clopidogrel.

When oral anticoagulation is recommended or suggested, the guidelines suggest using
a novel oral anticoagulant (NOAC) rather than adjusted-dose VKA therapy. When VKA
therapy is used, it is important to aim for good-quality anticoagulation control with
a time in therapeutic range that is greater than 70%.

Modifiable bleeding risk factors should be assessed with the HAS-BLED score at every
patient contact, and patients considered high-risk, defined as those with a score
of 3 or higher, can be identified for earlier review and follow-up visits.

Regarding surgical procedures and interventions, the guidelines suggest preoperative
management without bridging for patients with atrial fibrillation who are taking warfarin
and do not have a high risk for thromboembolism or a mechanical valve. In patients
with atrial fibrillation taking antithrombotic prophylaxis with warfarin who have
a high risk for thromboembolism or who do have a mechanical valve, preoperative management
with bridging is suggested. Preoperative management without bridging is suggested
in patients with atrial fibrillation who are taking a NOAC for antithrombotic prophylaxis,
but could be considered if the patient cannot take oral medications for a prolonged
period.

The guideline authors stressed that atrial fibrillation should not be considered in
isolation or at a single stage, such as detection, prevention, or treatment, and noted
that although most patients with the disorder die of cardiac causes, most interventions
focus on stroke prevention. They called for “a more holistic approach”
that considers comorbidities and cross-disease sequelae across primary and secondary
care.

ACP Hospitalist provides news and information for hospitalists, covering the major issues in the field. All published material, which is covered by copyright, represents the views of the contributor and does not reflect the opinion of the American College of Physicians or any other institution unless clearly stated.